Osteoarthritis (OA) is a common form of arthritis, a major cause of pain and disability in older adults. It is not merely a wear-and-tear process but involves abnormal remodeling of joint tissues driven by inflammatory mediators. Key risk factors include age, gender, prior joint injury, obesity, genetic predisposition, and mechanical factors. Pathological changes in OA joints include cartilage degradation, subchondral bone thickening, osteophyte formation, synovial inflammation, and ligament degeneration. These changes affect the entire joint structure, leading to pain, deformity, and loss of function. Articular cartilage is altered in OA, with early changes occurring in areas of high mechanical stress. Chondrocytes become activated, leading to increased production of matrix proteins and enzymes that degrade cartilage. Matrix-degrading enzymes such as aggrecanases and collagenases, along with inflammatory cytokines, contribute to cartilage breakdown. Mechanical stress and inflammatory stimuli activate pathways like NF-κB and MAPK, leading to the expression of genes involved in catabolic and inflammatory events. The menisci and ligaments in knee OA also show pathological changes, including matrix disruption, calcification, and cell death. These changes are associated with increased risk of OA and may contribute to joint pain. Subchondral bone undergoes remodeling in response to mechanical stress, with changes in bone volume and density reflecting prior loading history. Bone marrow lesions are often seen in OA and may be related to mechanical and traumatic factors. Synovial inflammation is present in many OA patients, with increased vascularity and inflammatory infiltrates. Synovitis is associated with cartilage damage and progression of OA. Inflammatory mediators such as cytokines and chemokines contribute to synovial inflammation and cartilage degradation. TLRs and complement pathways are involved in the inflammatory response in OA. OA is a complex disease involving multiple tissues and pathways. Understanding the interactions between these tissues is crucial for developing effective therapies. Current research highlights the role of mechanical factors, inflammatory mediators, and genetic and epigenetic mechanisms in OA pathogenesis. Advances in imaging and biomarkers are needed to better understand and treat OA. The disease is now viewed as a systemic process affecting the joint as an organ, requiring a systems approach to address its multifaceted nature.Osteoarthritis (OA) is a common form of arthritis, a major cause of pain and disability in older adults. It is not merely a wear-and-tear process but involves abnormal remodeling of joint tissues driven by inflammatory mediators. Key risk factors include age, gender, prior joint injury, obesity, genetic predisposition, and mechanical factors. Pathological changes in OA joints include cartilage degradation, subchondral bone thickening, osteophyte formation, synovial inflammation, and ligament degeneration. These changes affect the entire joint structure, leading to pain, deformity, and loss of function. Articular cartilage is altered in OA, with early changes occurring in areas of high mechanical stress. Chondrocytes become activated, leading to increased production of matrix proteins and enzymes that degrade cartilage. Matrix-degrading enzymes such as aggrecanases and collagenases, along with inflammatory cytokines, contribute to cartilage breakdown. Mechanical stress and inflammatory stimuli activate pathways like NF-κB and MAPK, leading to the expression of genes involved in catabolic and inflammatory events. The menisci and ligaments in knee OA also show pathological changes, including matrix disruption, calcification, and cell death. These changes are associated with increased risk of OA and may contribute to joint pain. Subchondral bone undergoes remodeling in response to mechanical stress, with changes in bone volume and density reflecting prior loading history. Bone marrow lesions are often seen in OA and may be related to mechanical and traumatic factors. Synovial inflammation is present in many OA patients, with increased vascularity and inflammatory infiltrates. Synovitis is associated with cartilage damage and progression of OA. Inflammatory mediators such as cytokines and chemokines contribute to synovial inflammation and cartilage degradation. TLRs and complement pathways are involved in the inflammatory response in OA. OA is a complex disease involving multiple tissues and pathways. Understanding the interactions between these tissues is crucial for developing effective therapies. Current research highlights the role of mechanical factors, inflammatory mediators, and genetic and epigenetic mechanisms in OA pathogenesis. Advances in imaging and biomarkers are needed to better understand and treat OA. The disease is now viewed as a systemic process affecting the joint as an organ, requiring a systems approach to address its multifaceted nature.